{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:03:30Z","timestamp":1791234210593,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,1,26]],"date-time":"2015-01-26T00:00:00Z","timestamp":1422230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004792","name":"MESR","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004792","id-type":"DOI","asserted-by":"crossref"}]},{"name":"LABEX SynOrg","award":["ANR-11-LABX-0029"],"award-info":[{"award-number":["ANR-11-LABX-0029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,5]]},"abstract":"Abstract<\/jats:title>The dual\u2010specificity tyrosine phosphorylation\u2010regulated kinase 1A (DYRK<\/jats:styled-content>1A) gene is located within the Down Syndrome (DS<\/jats:styled-content>) critical region on chromosome 21 and is implicated in the generation of Tau and amyloid pathologies that are associated with the early onset Alzheimer's Disease (AD<\/jats:styled-content>) observed in DS<\/jats:styled-content>. DYRK<\/jats:styled-content>1A is also found associated with neurofibrillary tangles in sporadic AD<\/jats:styled-content> and phosphorylates key AD<\/jats:styled-content> players (Tau, amyloid precursor, protein, etc). Thus, DYRK<\/jats:styled-content>1A may be an important therapeutic target to modify the course of Tau and amyloid beta (A\u03b2) pathologies. Here, we describe EHT 5372 (methyl 9\u2010(2,4\u2010dichlorophenylamino) thiazolo[5,4\u2010f]quinazoline\u20102\u2010carbimidate), a novel, highly potent (IC<\/jats:styled-content>50<\/jats:sub>\u00a0=\u00a00.22 nM<\/jats:styled-content>) DYRK<\/jats:styled-content>1A inhibitor with a high degree of selectivity over 339 kinases. Models in which inhibition of DYRK<\/jats:styled-content>1A by siRNA<\/jats:styled-content> reduced and DYRK<\/jats:styled-content>1A over\u2010expression induced Tau phosphorylation or A\u03b2 production were used. EHT<\/jats:styled-content> 5372 inhibits DYRK<\/jats:styled-content>1A\u2010induced Tau phosphorylation at multiple AD<\/jats:styled-content>\u2010relevant sites in biochemical and cellular assays. EHT<\/jats:styled-content> 5372 also normalizes both A\u03b2\u2010induced Tau phosphorylation and DYRK<\/jats:styled-content>1A\u2010stimulated A\u03b2 production. DYRK<\/jats:styled-content>1A is thus as a key element of A\u03b2\u2010mediated Tau hyperphosphorylation, which links Tau and amyloid pathologies. EHT<\/jats:styled-content> 5372 and other compounds in its class warrant in vivo<\/jats:italic> investigation as a novel, high\u2010potential therapy for AD<\/jats:styled-content> and other Tau opathies.\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p>Inhibition of the dual specificity tyrosine\u2010phosphorylation\u2010regulated kinase 1A (DYRK1A) is a new high\u2010potential therapeutic approach for Alzheimer disease. Here we describe EHT 5372, a novel potent and selective DYRK1A inhibitor. EHT 5372 inhibits DYRK1A\u2010induced Tau phosphorylation, A\u03b2 production and A\u03b2 effects on phospho\u2010Tau, including Tau aggregation.<\/jats:p>","DOI":"10.1111\/jnc.13018","type":"journal-article","created":{"date-parts":[[2014,12,30]],"date-time":"2014-12-30T07:39:05Z","timestamp":1419925145000},"page":"440-451","source":"Crossref","is-referenced-by-count":117,"title":["A novel DYRK1A (Dual specificity tyrosine phosphorylation\u2010regulated kinase 1A) inhibitor for the treatment of Alzheimer's disease: effect on Tau and amyloid pathologies in vitro<\/i>"],"prefix":"10.1111","volume":"133","author":[{"given":"S\u00e9verine","family":"Coutadeur","sequence":"first","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Benyamine","sequence":"additional","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Delalonde","sequence":"additional","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Leblond","sequence":"additional","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Foucourt","sequence":"additional","affiliation":[{"name":"Normandie Univ COBRA UMR 6014 & FR 3038; Univ Rouen; INSA Rouen; CNRS IRCOF 1 rue Tesni\u00e8re Mont St Aignan Cedex Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Besson","sequence":"additional","affiliation":[{"name":"Normandie Univ COBRA UMR 6014 & FR 3038; Univ Rouen; INSA Rouen; CNRS IRCOF 1 rue Tesni\u00e8re Mont St Aignan Cedex Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Sophie","family":"Casagrande","sequence":"additional","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Taverne","sequence":"additional","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lique","family":"Girard","sequence":"additional","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Pando","sequence":"additional","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"D\u00e9sir\u00e9","sequence":"additional","affiliation":[{"name":"Diaxonhit Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010100423"},{"key":"e_1_2_7_3_1","first-page":"11","article-title":"High\u2010content siRNA screening of the kinome identifies kinases involved in Alzheimer's disease\u2010related tau hyperphosphorylation","volume":"12","author":"Azorsa D. 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